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Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer.
BMC Cancer ( IF 3.8 ) Pub Date : 2019-12-30 , DOI: 10.1186/s12885-019-6470-y
Huiran Yue 1, 2 , Jieyu Wang 1, 2 , Ruifang Chen 1, 2 , Xiaoman Hou 1, 2 , Jun Li 1, 2 , Xin Lu 1, 2
Affiliation  

BACKGROUND The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer. METHODS Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases. RESULTS We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer. CONCLUSIONS Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

中文翻译:

基质浸润和活化升高的基因签名特征与浆液性卵巢癌发生血源性和淋巴转移的风险增加有关。

背景技术由于卵巢癌在腹膜内和远处转移的形成中起着必不可少的作用,因此在卵巢癌中血行和淋巴转移的临床意义已得到越来越多的关注。我们的目标是确定浆液性卵巢癌中与该相对较新的转移途径潜在相关的关键分子和生物学过程。方法由于淋巴管空间侵犯(LVSI)被认为是血行和淋巴扩散的第一步,因此我们主要基于转录组概况开发了基因签名,并在癌症基因组图谱(TCGA)数据集中提供了有关LVSI状态的可用信息。然后,我们使用多个公共数据库探索了所鉴定基因签名的潜在生物学原理和预后价值。结果我们观察到,具有血源性和淋巴转移风险增加的原发性肿瘤高度表达一组基因,即POSTN,LUM,THBS2,COL3A1,COL5A1,COL5A2,FAP1和FBN1。鉴定出的基因集的特征在于细胞外基质的沉积增强和广泛的基质激活。从机制上讲,基质细胞(尤其是成纤维细胞)的募集和激活均与淋巴管转移密切相关。生存分析进一步揭示,已鉴定基因的表达升高与浆液性卵巢癌患者的癌症进展和不良预后相关。结论我们的发现表明,肿瘤基质支持卵巢癌的血源性和淋巴性扩散,增加了肿瘤的侵袭性,并最终导致生存期恶化。
更新日期:2019-12-31
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